Apoptosis and Inflammation Involved with Fluoride-Induced Bone Injuries.

BACKGROUND: Excessive fluoride exposure induces skeletal fluorosis, but the specific mechanism responsible is still unclear. Therefore, this study aimed to identify the pathogenesis of fluoride-induced bone injuries. METHODS: We systematically searched fluoride-induced bone injury-related genes from five databases. Then, these genes were subjected to enrichment analyses. A TF (transcription factor)-mRNA-miRNA network and protein-protein interaction (PPI) network were constructed using Cytoscape, and the Human Protein Atlas (HPA) database was used to screen the expression of key proteins. The candidate pharmacological targets were predicted using the Drug Signature Database. RESULTS: A total of 85 studies were included in this study, and 112 osteoblast-, 35 osteoclast-, and 41 chondrocyte-related differential expression genes (DEGs) were identified. Functional enrichment analyses showed that the Atf4, Bcl2, Col1a1, Fgf21, Fgfr1 and Il6 genes were significantly enriched in the PI3K-Akt signaling pathway of osteoblasts, Mmp9 and Mmp13 genes were enriched in the IL-17 signaling pathway of osteoclasts, and Bmp2 and Bmp7 genes were enriched in the TGF-beta signaling pathway of chondrocytes. With the use of the TF-mRNA-miRNA network, the Col1a1, Bcl2, Fgfr1, Mmp9, Mmp13, Bmp2, and Bmp7 genes were identified as the key regulatory factors. Selenium methyl cysteine, CGS-27023A, and calcium phosphate were predicted to be the potential drugs for skeletal fluorosis. CONCLUSIONS: These results suggested that the PI3K-Akt signaling pathway being involved in the apoptosis of osteoblasts, with the IL-17 and the TGF-beta signaling pathways being involved in the inflammation of osteoclasts and chondrocytes in fluoride-induced bone injuries.

Severe magnitude of dental and skeletal fluorosis and its impact on society and environment in a part of Manbhum-Singhbhum Plateau, India.

BACKGROUND: Numerous approaches have been adopted to evaluate limited freshwater resources and the associated health hazards due to excessive amounts of fluoride in drinking water. The study aims to assess the degree and severity of dental and skeletal fluorosis and examine the broader effects of fluorosis on human health and society in the Manbhum-Singhbhum Plateau region, India. METHODS: The Community Fluorosis Index (CFI) and Dean's Index have been used to measure the magnitude and severity of dental and skeletal fluorosis. Questionnaire surveys, Focus Group Discussions (FGDs), and appropriate statistical methods have been applied to identify the social impacts. Risk-prone zones have been identified through overlay analysis using geoinformatics. RESULTS: About 54.60% of people in 67 villages of this part of the Manbhum-Singhbhum Plateau are affected in varying degrees of fluorosis ranging from very mild to mild, moderate, and severe dental fluorosis. Among these 67 villages, Janra (Manbazar I) and Hijla (Barabazar) have the most severely affected people. School dropout (n = 426), social isolation (n = 149), remarriage (n = 21), and physically disabled (n = 75) have also been reported. The study shows that about 414.29 km2 of the Manbhum-Singhbhum Plateau comes under the high-risk-prone category. CONCLUSIONS: The societal and environmental awareness of the fluorosis-affected individuals is almost absent in this region. Economic hardships, lack of education, inadequate health care facilities, water scarcity, and lack of awareness increase the magnitude of health hazards and societal vulnerability of the people in this region, who are largely dependent on natural resources.

Skeletal fluorosis: an uncommon cause, yet a rescue treatment?

PURPOSE: Skeletal fluorosis (SF) results from chronic exposure to fluoride (F-) causing excessive aberrantly mineralized brittle bone tissue, fractures, and exostoses. There is no established treatment other than avoiding the source of F-. Still, excess F- can persist in bone for decades after exposure ceases. CASE PRESENTATION: A 50-year-old woman presented with multiple, recurrent, low AQ2 trauma fractures yet high radiologic bone mineral density. Serum F- was elevated, and osteomalacia was documented by non-decalcified transiliac biopsy. She reported intermittently "huffing" a keyboard cleaner containing F- (difluoroethane) for years. Following cessation of her F- exposure, we evaluated the administration of the parathyroid hormone analog, abaloparatide, hoping to increase bone remodeling and diminish her skeletal F- burden. CONCLUSION: Due to the prolonged half-life of F- in bone, SF can cause fracturing long after F- exposure stops. Anabolic therapy approved for osteoporosis, such as abaloparatide, may induce mineralized bone turnover to replace the poorly mineralized osteomalacic bone characteristic of SF and thereby diminish fracture risk. Following abaloparatide treatment for our patient, there was a decrease in bone density as well as a reduction in F- levels.

Minocycline-Induced Black Bone Disease in Foot and Ankle Surgery: A Case Report.

BACKGROUND: Bone and periarticular tissue discoloration can be an unexpected finding that is often disconcerting for surgeons and may alter surgical plans and overall patient management. Common causes of bone discoloration include infection, avascular necrosis, and bone inflammation. Minocycline-induced black bone disease is a rare and relatively benign abnormality encountered in foot and ankle surgery that can cause significant black, blue, and gray discoloration of bone. METHODS: Unanticipated intraoperative findings of diffuse black, blue, and gray bone discoloration during an elective forefoot operation raised concern for a metabolically malignant process and prompted the conversion of plans for a first metatarsophalangeal joint implant arthroplasty to a Keller arthroplasty. The plan for proximal interphalangeal joint arthroplasties of the lesser digits were continued as planned. Bone specimens were sent for pathologic analysis. RESULTS: Postoperative analysis identified chronic use of a minocycline for acne vulgaris. Pathologic analysis of the specimens ruled out malignant processes. Altogether, the data available led to the diagnosis of minocycline-induced black bone disease. Since the last follow-up, the patient has healed well without complications. CONCLUSIONS: Our case report underscores the importance of including the chronic use of tetracyclines in medical history intake during preoperative visits to assist the surgeon in intraoperative decision-making.

Radiographical bony lesions after discontinuation of immunosuppressant therapy: bone involvement in sarcoidosis.

We describe a patient who had failed renal transplant after 13 years, eventually requiring a graft nephrectomy and discontinuation of immunosuppressive therapy, including antithymocyte globulin, tacrolimus and mycophenolate while on steroid avoidance protocol. Within a few months of complete discontinuation of the immunosuppressive medications, she developed lower back pain associated with numbness in her right anterolateral thigh. The radiological imaging demonstrated multiple bony lesions throughout her axial and appendicular skeleton with normal pulmonary findings. A computerised tomography-guided bone biopsy from the left iliac crest revealed fragments of bone with granulomatous inflammation, thus making the diagnosis of extrapulmonary sarcoidosis. Initiating treatment with prednisone resulted in near-complete resolution of symptoms. Long-term immunosuppressive therapy is administered to all renal transplant recipients to help prevent acute rejection and loss of renal allograft. This case highlights that immunosuppressants can conceal the presence of underlying conditions in transplant patients.

Effect of Loratadine for Pegfilgrastim-Induced Bone Pain.

AIMS: Breast cancer patients on chemotherapy who receive pegfilgrastim to prevent neutropenia may experience severe bone pain as a side effect. Traditional treatment recommendations include nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, and/or antihistamine use. However, little research was found comparing these interventions. The study aim was to address the gaps in literature and to explore the use of and perceived effectiveness of loratadine versus acetaminophen or NSAIDs in women with breast cancer treated with pegfilgrastim. This study also sought to understand how patients became aware of loratadine or other treatments for management of bone pain. DESIGN/METHODS: This cross-sectional study used survey methods to collect data from 66 adult female breast cancer patients receiving chemotherapy with pegfilgrastim. RESULTS: The incidence of bone pain was 45% (n = 30) in our sample, but more than half (n = 45; 69%) of the women took either acetaminophen, NSAIDs, or loratadine alone or in combination to prevent bone pain. All medication were rated as effective by patients, with acetaminophen slightly more effective than loratadine, and loratadine more effective than NSAIDs. CONCLUSIONS: Acetaminophen, NSAIDs, and loratadine are easily available and inexpensive. However, unlike acetaminophen and NSAIDs, loratadine is dosed once a day and well tolerated with minimal adverse effects. CLINICAL IMPLICATIONS: Randomized controlled trials are needed to adequately assess the effectiveness of all three medication options. Because little is known about optimal use of any of these medications for pegfilgrastim-induced bone pain, it is also important to identify the optimal time to initiate treatment and ideal treatment duration.

Impaired bone health as a co-morbidity of epilepsy.

Increasing number of studies shows significant reductions in bone mineral density in patients with epilepsy treated with enzyme-inducing anti-seizure medications (EIASM), valproic acid, and newer anti-seizure medications (ASM). ASM seems to be a specific risk factor for the development of osteoporosis affecting 11%-31% of patients with epilepsy and leads to 2 to 6 times increased risk of fractures compared to the background population. Treatment with ASM clearly contributes to epilepsy-associated bone disease. Yet, the exact pathophysiological mechanism has not been established; however, several hypotheses were suggested, especially in relation to EIASM. As the long-lasting medical treatment, often in polytherapy, has shown negative effects on bone health, it indicates the need for guidelines for the prevention and management of bone disease to be included in the follow-up of patients with epilepsy. An algorithm for following bone status during the treatment has been suggested based on Danish national guidelines.

Clinical features of methotrexate osteopathy in rheumatic musculoskeletal disease: A systematic review.

BACKGROUND: There is growing evidence from case reports that methotrexate (MTX) therapy may impair bone metabolism in individual patients leading to low bone mass, atraumatic stress fractures and immobilizing bone pain - referred to as 'MTX osteopathy'. However, the clinical features, risk factors and treatment options of this condition are still elusive. METHODS: A systematic review was conducted according to PRISMA guidelines. Two databases (MEDLINE, Embase) were searched for published cases of MTX osteopathy in patients with rheumatic musculoskeletal diseases (RMD). Data from the included publications were extracted and descriptive statistical analysis was performed. RESULTS: We report data from 32 studies describing 80 adult RMD patients with stress fractures in MTX osteopathy. Most cases were found in elderly women with longstanding RMD, especially rheumatoid arthritis (72.5%). MTX osteopathy commonly presented as stress fracture of the distal tibia (51.3%), calcaneus (35.0%) and proximal tibia (27.5%), mimicking arthritis in some cases. Although a majority of the patients met the densitometric criteria for osteoporosis (58.1%), typical osteoporotic fractures (e.g., vertebral fractures) were rarely seen. Patients frequently suffered from bilateral (55.0%), multiple (71.3%) and recurrent fractures (25.0%). Fractures mainly occurred at low to moderate doses of MTX therapy (45.0%). It should be noted that half (48.8%) of the patients did not receive systemic steroid therapy for at least 3 years. CONCLUSIONS: Low-dose MTX therapy in RMD may result in atraumatic stress fractures of the lower extremity that can mimic arthritis. MTX osteopathy is characterized by a pathognomonic type of stress fractures with band- or meander-shaped appearance along the growth plate.

Multidisciplinary Multiagent Treatment of Complex Lymphatic Anomalies with Severe Bone Disease: A Single-Site Experience.

Background: Complex lymphatic anomalies (CLA) are a group of conditions that pose diagnostic and therapeutic challenges due to their rarity and overlapping clinical findings. This case series describes the complex pathology and novel combination therapies of three patients diagnosed with various types of CLA. Methods and Results: A retrospective review of medical records was performed for three patients treated for CLA between 2011 and 2019. Diagnostics, imaging, treatment, and follow-up were reviewed in the electronic medical record and combined with the literature review within the analysis. One patient had involvement of her skull base and ear canals, diagnosed after ear canal abnormalities were detected on computed tomography following meningitis. The second patient had involvement of her posterior ribs and T7-T12 vertebral bodies, with thoracic instability requiring a back brace. The third patient had involvement of his left lower extremity and hemipelvis, necessitating a left above the knee amputation. Case 1 progressed on sirolimus and pamidronate but responded to zoledronic acid (ZA). She developed flares of coagulopathy and cellulitis that required reinforcement with vincristine and steroid pulses. Similarly, case 2 progressed on sirolimus and ZA alone, but achieved stable disease with added vincristine. Upon further disease progression, stabilization was obtained by the reinforcement of ZA. Case 3 required a combination of surgery as well as medical management with sirolimus and pamidronate. All three patients now have stable disease. Conclusion: This case series depicts a multidisciplinary and multiagent approach to the management of CLA with severe bony involvement using sirolimus, bisphosphonates, vincristine, and steroids.

A comprehensive review on endemic and experimental fluorosis in sheep: Its diverse effects and prevention.

Fluoride is a natural element widely distributed in the environment and plays an important role in the growth of humans and animals. However, in many species, high concentrations of fluoride induce several problems, such as dental, skeletal, and non-skeletal fluorosis. Sheep living in endemic areas are sensitive to the chronic toxicity of fluoride, and they have been found to suffer not only from teeth and bone problems but also from other organs. Studies indicating the chronic harmful effects of fluoride on teeth, bones, blood biochemical parameters, kidney, liver, heart, reproductive system and growth in sheep have been clearly summarized in this review. Besides, this work also includes updated progress in terms of prevention or reduction of fluoride toxicity in this species.

Blood lead levels, calcium metabolism and bone-turnover among automobile technicians in Sagamu, Nigeria: Implications for elevated risk of susceptibility to bone diseases.

Lead is an occupational toxicant and a recognised health threat particularly in developing countries. Hence, this study explored the interaction of blood lead level (BLL), a conventional marker of lead exposure, with indices of calcium metabolism and biomarkers of bone-turnover in 120 adult male automobile technicians (AT) with ≥ 1 year duration in professional practice. The AT as well as the control group, which comprised 120 age, body-size and socio-economically matched male administrative workers, were recruited from Sagamu, South West Nigeria. Levels of blood lead, serum indices of calcium metabolism [total calcium (tCa), ionised calcium (iCa), phosphate, albumin, magnesium (Mg) and 25-Hydroxycholecalceferol (25-OHCC)], biomarkers of bone formation [bone alkaline phosphatase (BALP) and osteocalcin (OC)] and biomarkers of bone resorption [tartarate-resistant acid phosphatase-5b (TACRP-5b) and urinary hydroxyproline (UHYP)] were determined in all participants. The BLL, 25-OHCC, TRACP-5b and UHYP significantly increased while tCa and iCa significantly reduced in AT compared to control. However, no significant difference was observed in phosphate, albumin, Mg, BALP and OC in AT compared to control. Interestingly, BLL demonstrated a significant negative association with tCa and iCa but a significant positive association with 25-OHCC, TRACP-5b and UHYP. However, BLL did not show significant association with phosphate, albumin, Mg, BALP and OC. Increased lead exposure as well as altered calcium metabolism and bone-turnover demonstrated by the automobile technicians may be suggestive of lead-induced accelerated bone demineralisation. These workers may be predisposed to high risk of increased susceptibility to bone diseases if this sub-clinical picture is sustained.

Minocycline black bone disease in arthroplasty: a systematic review.

BACKGROUND: Minocycline black bone disease is a rare finding that can cause concern when unexpectedly encountered during routine arthroplasty. Prolonged minocycline use can cause selective staining of subchondral bone, whilst peri-articular soft tissue and cartilage appear uninvolved. METHODS: A systematic review according to PRISMA guidelines was performed to identify all reported cases in the literature. RESULTS: Including the patient we present, eleven cases of minocycline black bone disease encountered during arthroplasty have been reported in the literature. All cases have had an excellent outcome, with no complications reported to date. CONCLUSIONS: Minocycline black bone disease can be a concerning intra-operative finding when unexpectedly encountered during routine arthroplasty, but should not affect the operative plan. Surgeons should exclude alternative causes of bone discolouration when the history is unclear.

The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury.

OBJECTIVE: This study was designed to observe the expression of important hedgehog (Hh) signal factors in the bone tissue of rats with chronic fluorosis and cultured osteoblasts in order to investigate the role and significance of the Hh signal in fluoride-induced bone injury. METHODS: Healthy Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the fluorosis group (F Group), the fluoride + blocker group (F + Cycl group: rats were treated with fluoride + cyclopamine), and the fluoride + blocker control group (F + DMSO group). After 6 months of intervention, the urinary fluoride content of rats in each group was detected. The primary osteoblasts of rats were selected for cell experiment, and the experiment was carried out after the cells were passaged from the second to the fourth generation. RESULTS: The proliferation rate of primary rat osteoblasts presented time-affected and dose-affected relationships in a short time under treatment with a low dose of sodium fluoride (NaF), but the proliferation of osteoblasts was inhibited by long-term and high-dose NaF exposure. In the F group, the alkaline phosphatase (ALP) activity of osteoblasts increased gradually. The ALP activity was lower in the F + Cycl group than in the F group, and there was no significant difference between the F + DMSO group and F group. With the increase in fluoride exposure, the expression of Hh signal factors and osteogenic-related factor proteins increased gradually. The expressions of Indian hedgehog (Ihh), smoothened (Smo), Glioma-associated oncogene homolog (Gli) 2, and Runt-related transcription factor 2 (Runx2)in the F + Cycl group increased with the dose of fluoride but they were significantly inhibited compared with the F group. Compared with the control group, the content of urinary fluoride in the F group was significantly higher (P < 0.05), but there was no significant change in urinary fluoride content in the F + Cycl group and the F + DMSO group. Compared with the control group, the serum bone alkaline phosphatase (BALP) contents of rats in the other groups increased after 6 months' intake of fluoride water (P < 0.05). After drug blocking, the serum BALP content in the F + Cycl group was lower than that in the F + DMSO group (P < 0.05). The BALP content in the F + DMSO group was similar to that in the F group: it did not decrease. The mRNA expressions of Ihh, Smo, Gli2, and Runx2 in bone tissue of the F group were significantly higher than those in the control group (P < 0.05). After cyclopamine blocking, the expressions decreased (P < 0.05), but the differences between the F + DMSO group and F group were not statistically significant. CONCLUSION: Hh signal plays an important role in fluoride-induced bone injury. The effective inhibition of cyclopamine is expected to be a new target for the treatment of skeletal damage caused by fluorosis.

Non-endemic skeletal fluorosis: Causes and associated secondary hyperparathyroidism (case report and literature review).

Skeletal fluorosis (SF) is endemic primarily in regions with fluoride (F)-contaminated well water, but can reflect other types of chronic F exposure. Calcium (Ca) and vitamin D (D) deficiency can exacerbate SF. A 51-year-old man with years of musculoskeletal pain and opiate use was hypocalcemic with secondary hyperparathyroidism upon manifesting recurrent long bone fractures. He smoked cigarettes, drank large amounts of cola beverage, and consumed little dietary Ca. Then, after 5 months of Ca and D3 supplementation, serum 25(OH)D was 21 ng/mL (Nl, 30-100), corrected serum Ca had normalized from 7.8 to 9.4 mg/dL (Nl, 8.5-10.1), alkaline phosphatase (ALP) had decreased from 1080 to 539 U/L (Nl, 46-116), yet parathyroid hormone (PTH) had increased from 133 to 327 pg/mL (Nl, 8.7-77.1). Radiographs revealed generalized osteosclerosis and a cystic lesion in a proximal femur. DXA BMD Z-scores were +7.4 and +0.4 at the lumbar spine and "1/3" radius, respectively. Bone scintigraphy showed increased uptake in two ribs, periarticular areas, and proximal left femur at the site of a subsequent atraumatic fracture. Elevated serum collagen type I C-telopeptide 2513 pg/mL (Nl, 87-345) and osteocalcin >300 ng/mL (Nl, 9-38) indicated rapid bone turnover. Negative studies included hepatitis C Ab, prostate-specific antigen, serum and urine electrophoresis, and Ion Torrent mutation analysis for dense or high-turnover skeletal diseases. After discovering markedly elevated F concentrations in his plasma [4.84 mg/L (Nl, 0.02-0.08)] and spot urine [42.6 mg/L (Nl, 0.2-3.2)], a two-year history emerged of "huffing" computer cleaner containing difluoroethane. Non-decalcified histology of a subsequent right femur fracture showed increased osteoblasts and osteoclasts and excessive osteoid. A 24-hour urine collection contained 27 mg/L F (Nl, 0.2-3.2) and <2 mg/dL Ca. Then, 19 months after "huffing" cessation and improved Ca and D3 intake, yet with persisting bone pain, serum PTH was normal (52 pg/mL) and serum ALP and urine F had decreased to 248 U/L and 3.3 mg/L, respectively. Our experience combined with 15 publications in PubMed concerning unusual causes of non-endemic SF where the F source became known (19 cases in all) revealed: 11 instances from high consumption of black tea and/or F-containing toothpaste, 1 due to geophagia of F-rich soil, and 7 due to "recreational" inhalation of F-containing vapors. Circulating PTH measured in 14 was substantially elevated in 2 (including ours) and mildly increased in 2. The severity of SF in the cases reviewed seemed to reflect cumulative F exposure, renal function, and Ca and D status. Several factors appeared to influence our patient's skeletal disease: i) direct anabolic effects of toxic amounts of F on his skeleton, ii) secondary hyperparathyroidism from degradation-resistant fluorapatite bone crystals and low dietary Ca, and iii) impaired mineralization of excessive osteoid due to hypocalcemia.

Skeletal pathology and bone mineral density changes in wild muskrats (Ondatra zibethicus) and red squirrels (Tamiasciurus hudsonicus) inhabiting arsenic polluted areas of Yellowknife, Northwest Territories (Canada): A radiographic densitometry study.

The City of Yellowknife is a known hotspot of arsenic contamination and there is a growing body of evidence suggesting that local wildlife in the vicinity of the abandoned Giant Mine site may be at risk of decreased bone mineralization and various bone disorders. The purpose of this study was to preliminarily measure bone mineral density (BMD) changes and investigate the incidence, pattern, and severity of bone lesions in wild muskrats and red squirrels breeding in three (3) catchment areas at different distances from the Giant Mine Site in Yellowknife, Northwest Territories (Canada): ~2 km (location 1), ~18 km (location 2), and ~40-100 km (location 3). Full femoral bones of 15 muskrats and 15 red squirrels were collected from the three sampling locations (5 from each location) and subjected to radiographic analysis and densitometric measurements. The patterns and severities of bone lesions, including changes in bone mineral density, were evaluated and compared between groups. As levels were significantly higher in the bones of muskrats caught from location 1 and 2, relative to location 3. Further, As and Cd levels were significantly higher in the bones of squirrels caught from locations 1 and 2 relative to squirrels caught from location 3. The preliminary results from bones revealed that radiographic abnormalities such as bone rarefaction, osteopenia, and thinning of the femoral shafts with significant ossific cystic lesions and bowing were the most common skeletal pathologies found in bones of red squirrels from the three locations. Radiographic appearances of massive sclerosis and dysplasia, including severe osteocondensation and osteopathia striata-like abnormalities, were found in the bones of muskrats from all the sampling locations. Densitometric evaluation showed no significant differences between the three locations in the bone parameters measured. However, there was a statistically significant correlation between As content in the bones of muskrats and percent fat content in the femur samples, which suggests that accumulation of As could have been a causal factor for a change in percent fat in femurs of muskrats.

Management of bone and metabolic effects of androgen deprivation therapy.

Androgen deprivation therapy (ADT) is commonly given to men with prostate cancer. Both its benefits as well as its adverse effects are a direct consequence of sex steroid withdrawal. While ADT improves oncologic outcomes in appropriately selected men, it is associated with adverse effects, including accelerated bone loss leading to increased fracture risk, and with metabolically unfavorable body composition changes that predispose to diabetes and may increase cardiovascular risk. In this review, we will describe the pathophysiology behind these ADT-associated adverse effects, and discuss the clinical evidence guiding clinical assessment and management. A proactive approach is important to minimize ADT-associated adverse sequelae, so that the benefit-risk ratio of this treatment is optimized.

Bone health effects of androgen-deprivation therapy and androgen receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer.

BACKGROUND: Osteoporosis is a skeletal disorder characterized by compromised bone strength, resulting in increased fracture risk. Patients with prostate cancer may have multiple risk factors contributing to bone fragility: advanced age, hypogonadism, and long-term use of androgen-deprivation therapy. Despite absence of metastatic disease, patients with nonmetastatic castrate-resistant prostate cancer receiving newer androgen receptor inhibitors can experience decreased bone mineral density. A systematic approach to bone health care has been hampered by a simplistic view that does not account for heterogeneity among prostate cancer patients or treatments they receive. This review aims to raise awareness in oncology and urology communities regarding the complexity of bone health, and to provide a framework for management strategies for patients with nonmetastatic castrate-resistant prostate cancer receiving androgen receptor inhibitor treatment. METHODS: We searched peer-reviewed literature on the PubMed database using key words "androgen-deprivation therapy," "androgen receptor inhibitors," "bone," "bone complications," and "nonmetastatic prostate cancer" from 2000 to present. RESULTS: We discuss how androgen inhibition affects bone health in patients with nonmetastatic castrate-resistant prostate cancer. We present data from phase 3 trials on the three approved androgen receptor inhibitors with regard to effects on bone. Finally, we present management strategies for maintenance of bone health. CONCLUSIONS: In patients with nonmetastatic castrate-resistant prostate cancer, aging, and antiandrogen therapy contribute to bone fragility. Newer androgen receptor inhibitors were associated with falls or fractures in a small subset of patients. Management guidelines include regular assessment of bone density, nutritional guidance, and use of antiresorptive bone health agents when warranted.

Bone Health in Childhood Chronic Disease.

Many children with chronic disease are now surviving into adulthood. As a result, there is a growing interest in optimizing bone health early in the disease course with the dual goals of improving quality of life during childhood and reducing life-long fracture risk. Risk factors for impaired bone health in these children include immobility, nutritional deficiency, exposure to bone toxic therapies, hormonal deficiencies affecting growth and pubertal development, and chronic inflammation. This review focuses on the chronic diseases of childhood most commonly associated with impaired bone health. Recent research findings and clinical practice recommendations, when available, for specific disorders are summarized.

Clinical Care of Bone Health in Patients on the Immune Tolerance Induction's Protocols With an Immunosuppressive Agent for Inhibitor Eradication in Hemophilia.

Nowadays, the development of factor VIII and IX inhibitors in patients with hemophilia is considered as the most challenging in the treatment of hemophilia. Immune tolerance induction (ITI) therapy is an approach for eradication of inhibitors. Some ITI protocols are routinely in use for the eradication of inhibitors in patients with hemophilia. Moreover, such a therapeutic regimen may facilitate the tendency to reduced bone density in patients with inhibitor. This study scheduled to investigate whether that predisposing role of ITI protocols with an immunosuppressive agent has considered or not. By a literature review, published ITI protocols in hemophilia with inhibitors were evaluated. Among them, 51 papers found and studied thoroughly. None of them had performed the bone mineral examination in patients with hemophilia and inhibitor under treatment. Since there are 2 coexisting facilitating factors in these protocols, considering the bone mineral density study for patients with inhibitor who are undergoing ITI protocols with an immunosuppressive agent is recommended.

Black bone syndrome in broilers fed ethanolic extract of mango seeds.

This study aimed to evaluate the incidence of black bone syndrome (BBS) in broiler chickens fed with ethanolic extract of mango seed (EEMS). A total of 504 one-day-old male broilers were used in a completely randomised design assigned with 7 experimental diets and 6 replicates of 12 broilers per experimental plot. The experimental diets consisted of: diet without addition of synthetic antioxidant; diet with addition of synthetic antioxidant (200 ppm); and 5 levels of EEMS: 200 ppm, 400 ppm, 600 ppm, 800 ppm, and 1,000 ppm. Two methods of cooking (roasted and boiled) were used to prepare thigh samples. According to the results, the diets did not significantly influence the performance of the broilers. BBS incidence was higher in broilers fed a diet without antioxidants and was reduced with EEMS dietary inclusion, with the lowest incidence occurring with the inclusion of 1,000 ppm. The synthetic antioxidant butylated hydroxytoluene in the diet promoted a significantly higher BBS incidence than that obtained with 800 and 1,000 ppm EEMS and did not differ from the other diets. Of the cooking methods, a higher BBS incidence was observed for the boiled method. For the meat coloration and bone parameters, there were no significant interactions between the factors, diets and cooking methods. There was a linear reduction in the darkening score and linear increase in the luminosity (L∗) of the meat with increasing EEMS in the diet. With regard to the cooking method, the boiled thighs had lower luminosity (L∗), higher parameter a∗, and lower parameter b∗ values because of more pronounced meat darkening. The roasted bones were less heavy, dense, and flexible. A negative correlation was observed between the degree of darkening of the meat that characterizes the BBS with the luminosity (L∗) and intensity of yellow. We concluded that the addition of EEMS contributes to a reduced darkening of meat that characterises the BBS and recommend the dietary inclusion of 1,000-ppm EEMS.